THE NANO PERESTROIKA

01-January-2018

RAJGOPAL NIDAMBOOR

The idea of nanomachines was first postulated by Richard Feynman, PhD, avant-garde physicist and Nobel-laureate. He hypothesised that there was ample ‘Room at the Bottom.’ He also suggested that human beings were a marvellous biological system — adept at doing things ‘small as big.’ He was far ahead of his time — he was not only dreaming of scientific fantasy, but also eventuality. His vision bid fair to the idea of potential medical applications of nanotechnology — of a programmable nanorobot exhibiting and working on the same page as proteins and cells. Better still, they could be fabricated and introduced into our bodily systems. You get the picture — of petite-sized soldiers of health, or nanomolecules of medicine, roaming the bloodstream, exterminating cancer cells, or slowing down the process of aging, among other things.

Recent advances in medical science attest to the fact that most illnesses originate from malfunctioning cells. The destiny of our micron-size cells is, in turn, determined by nanosize molecules — genes and proteins — residing within the cells. All the more reason why nanomedicine targets its ‘small but big’ ammo at specific locations within the cells. Conventional drugs, due to their micron-scale size, do not have such abilities — to pass through certain biological barriers. Nanomedicine is novel — it has the capability to pass through various biologic barriers and acquire access to molecules within specific cell compartments.

It goes without saying that nanomaterials, or particles, used in nanomedicine have several unique features unlike conventional micron-size materials. They not only have a tall ratio of surface area to volume — this enables the high loading of drugs on nanomaterial carriers. They also have the wherewithal to encapsulate dozens of drug molecules inside a single vehicle and direct the release of multiple drugs. In addition, tiny nanomaterials and particles have revolutionised, refined and redefined medical imaging techniques — at the optical, electronic, magnetic and biological levels.

Let us cull an example — when nanoparticles are directed at cancer cells, they release drug molecules to treat the cells. Besides, they also have the ability to emit light and heat to destroy such cells. This is achieved in a precise, incremental manner — while reducing the damage to healthy cells. You’d call it specific targeting with the added advantage of improved availability and release in a controlled, ‘customised,’ or bespoke manner. New nanomedicine research is also geared to develop new ways to improve nanoparticles’ biocompatibility and protect them from immune attack, guide them to diseased cells and, most importantly, enable oral administration methods for nanomedicine that can pass through the gastrointestinal tract, or barrier, without ado.

The most significant advantage of nanomedicine is iron oxide nanoparticles — to pick another example — which can be encrusted with a peptide and targeted to ‘hit’ a cancer tumour. The iron oxide nanoparticles can also enhance magnetic resonance imaging [MRI]. The best part is all electrons in iron oxide nanoparticles — which are less than 20nm — whirl in the same direction. The result is the overall magnetic-field strength is larger and more localised than that of larger drug particles. The larger magnetic field not only augments MRI, but also enables the nanoparticles in imaging to be easily taken up by tumour cells, while diffusing out the tumour itself more slowly — for much better analyses, or interpretation.

The use of iron oxide nanoparticles has been approved for liver imaging and in the early diagnosis of heart disease too, such as atherosclerosis, or hardening and narrowing of the arteries — the [in]famous trigger for heart attack and stroke. What’s more, such nanoparticles can accumulate specifically in the diseased area of the arteries and enable clinicians to monitor the development of arterial plaques, not to speak of their ‘disappearance’ following treatment. The use of nanoparticles has also extended to rapid detection tests for pregnancy, ovulation, flu and HIV virus, including neurological illnesses, among other disorders.

In addition, nanoparticles can destroy cells using apoptosis, or programmed cell death, or become naturally responsive — in other words, their behaviour in the area of drug release can be controlled by local stimuli like pH, or acid-base balance, temperature, chemical ‘prompts,’ or remote stimuli like electrical and magnetic fields. To highlight an exemplar — when nanoparticle carriers are made of pH-sensitive polymers, their release into different locations of the gastrointestinal tract can be controlled. This would be a big-plus, because pH conditions vary ad infinitum in the gut — the temple of good health and optimal wellness.

You may well ask as to what is the significance of such delivery modes. First, nanoparticle carriers are made with formulations of timed degraded polymers, including antibodies. This means that drugs can discharge into the colon 3-4 hours after leaving the stomach. When nanoparticle carriers are made of microbially degradable polymers, they can be ‘dispatched’ to the colon by specific colonic bacteria too. Think of programmed drug delivery and this is it — in all its therapeutic finesse and grandeur.

From the restorative angle, nanostructured materials have been used to regenerate bone, cartilage, vascular, bladder, nervous systems, muscle, skin and other tissues. Besides, ‘nanocoatings’ have been successfully used as dental implants, hip and intervertebral casings, besides stem cell encapsulation. What is most fascinating today is tissue regeneration — both in terms of diagnostics and regenerative therapeutic medicine.

All is not hunky-dory for programmed nanomedicine, though. Research has corroborated the existence of two major concerns and their resolution as regards the use of nanoparticles as drug carriers. The first is aimed to prevent phagocytosis, or foreign body removal by the immune system. To overcome the drawback, nanoparticles are usually coated by polymers, as cited earlier — this technique prolongs circulation time and bioavailability of drugs. However, on the downside, it may lead to the risk of over-accumulation in organs and tissues. Two, the distribution of nanoparticles within our body is, by and large, uninhibited and their effects on different tissues and organs are not yet fully understood.

It is suggested that nanoparticles of 20-50nm could enter healthy cells and the central nervous system [CNS]; particles smaller than 70nm can, likewise, enter the pulmonary system. Is there a way out? There is. When nanoparticles are, by design, formulated and ‘coached’ to specifically use their capability of penetrating biological barriers, they can overcome such obstacles. However, this should be deemed as an advantage for drug delivery and a hazard for inflammatory and other processes. In other words, it can hamper drug delivery and human physiology, including the natural ability of the body to heal itself — from the inside out — with a little help from medical treatment. Research is now on, in full swing, to correct the snag and perfect the nanoparticle therapeutic orchestra.

The emergence of new nanotechnology-based tools, methods and materials have also brought about a medical perestroika — it has taken diagnosis to a new level, while minimising the amount of biological samples. This has had a healthy cascading effect — on our environment and sustainability — thanks to a huge drop in the use of reagents, disposables and other lab paraphernalia. You guessed it right. The compact repertoire of nanosensors, instruments and nanomonitoring devices allow access to our body for diagnosis and therapy with a significantly reduced degree of invasive flourish. Nanomedicine researchers aver that new nanomaterials that are now available, or in the works, are excellent vehicles as diagnostic markers and drugs, because they are endowed with a new-fangled, advanced form of therapeutic ability and functionality. Besides, they are more resilient and biocompatible than conventional implants. They are perched at the altar of futuristic medicine to ‘perk up’ diagnostics, therapeutic delivery and exactitude of medical treatment, while limiting the harmful side-effects of modern drugs and surgical interventions.

The nanomedicine approach is poised to revolutionise medicine and lead to a giant leap in treating a host of disorders, big and small, that have no easy, or long-term, curative answers. To highlight some examples — myocardial infarction and stroke, cancer and inflammatory disease, among others. Hospital admission and treatment are too protracted and not always beneficial for such patients and their care-givers. The potential that nanomedicine offers for their early diagnosis and treatment will, therefore, be a boon. It will not only transform monitoring of patients in critical conditions in intensive care units [ICU], but also usher in the use of ‘customised’ therapies that specifically target the diseased organs and cells, while curtailing or annulling the influx of side-effects — some of them being serious or worse than the original disease.

Vaccine delivery with nanomedicine is another great, new frontier — it ‘engineers’ a stronger and more powerful immune response. Research is also on to direct the release of insulin with the aid of a sponge-like matrix that contains the peptide hormone as well as nanocapsules with therapeutic enzymes. This is how it works — when blood sugar levels shoot up in diabetics, the nanocapsules release hydrogen ions. The ions bind to fibres making up the matrix — in so doing, the ions defy each other and generate openings, in the matrix, through which insulin is released.

The arrival of a new ‘chill pill,’ a nanoparticle that could be taken orally and can also pass effortlessly through the lining of the intestines into the bloodsteam is yet another exciting therapeutic tool. The advance will allow drugs that must now be delivered with a shot in an easy-to-swallow pill form. New research is on to develop nanoparticles that can deliver drugs across the brain barrier to treat neurological disorders, such as Alzheimer’s and Parkinson’s disease too. Research is in progress to ‘mounting’ a nanoparticle to beat viruses, or viral incursions. The nanoparticle is not aimed to literally destroy viruses. It is ‘filled and armed’ with an enzyme that delivers the ‘knock-out’ punch — while eliminating the replication of virus molecules in the patient’s bloodstream — including the possibility of infecting another, or experiencing a nasty relapse.